Patterns of osteocytic endothelial nitric oxide synthase expression in the femoral neck cortex: Differences between cases of intracapsular hip fracture and controls

Evidence indicates that extensive amalgamation of adjacent resorbing osteons is responsible for destroying the microstructural integrity of the femoral neck's inferior cortex in osteoporotic hip fracture. Such osteonal amalgamation is likely to involve a failure to limit excessive resorption, but its mechanistic basis remains enigmatic. Nitric oxide (NO) inhibits osteoclastic bone destruction, and in normal bone cells its generation by endothelial nitric oxide synthase (eNOS, the predominant bone isoform) is enhanced by mechanical stimuli and estrogen, which both protect against fracture. To determine whether eNOS expression in osteocytes reflects their proposed role in regulating remodeling, we have examined patterns of osteocyte eNOS immunolabeling in the femoral neck cortex of seven cases of hip fracture and seven controls (females aged 68-96 years). The density of eNOS+ cells (mm(-2)) was 53% lower in the inferior cortex of the fracture cases (p < 0.0004), but was similar in the superior cortex. eNOS+ osteocytes were, on average, 22% further from their nearest blood supply, than osteocytes in general (p < 0.0001) and the nearest eNOS+ osteocyte was 57% further from its nearest canal surface (p < 0.0001). This differential distribution of eNOS+ osteocytes was significantly more pronounced in the cortices of fracture cases (p < 0.0001). We conclude that the normal regional and osteonal pattern of eNOS expression by osteocytes is disrupted in hip fracture, particularly at sites that are loaded most by physical activity. These results suggest that eNOS+ osteocytes may normally act as sentinels confining resorption within single osteons. A reduction in their number, coupled to an increase in their remoteness from canal surfaces, may thus permit the irreversible merging of resorbing osteons, and thus contribute to the marked increase in the fragility of osteoporotic bone

The impact of stapling technique and surgeon specialism on anastomotic failure after right?sided colorectal resection: an international multicentre, prospective audit

Aim There is little evidence to support choice of technique and configuration for stapled anastomoses after right hemicolectomy and ileocaecal resection. This study aimed to determine the relationship between stapling technique and anastomotic failure. Method Any unit performing gastrointestinal surgery was invited to contribute data on consecutive adult patients undergoing right hemicolectomy or ileocolic resection to this prospective, observational, international, multicentre study. Patients undergoing stapled, side?to?side ileocolic anastomoses were identified and multilevel, multivariable logistic regression analyses were performed to explore factors associated with anastomotic leak. Results One thousand three hundred and forty?seven patients were included from 200 centres in 32 countries. The overall anastomotic leak rate was 8.3%. Upon multivariate analysis there was no difference in leak rate with use of a cutting stapler for apical closure compared with a noncutting stapler (8.4% vs 8.0%, OR 0.91, 95% CI 0.54–1.53, P = 0.72). Oversewing of the apical staple line, whether in the cutting group (7.9% vs 9.7%, OR 0.87, 95% CI 0.52–1.46, P = 0.60) or noncutting group (8.9% vs 5.7%, OR 1.40, 95% CI 0.46–4.23, P = 0.55) also conferred no benefit in terms of reducing leak rates. Surgeons reporting to be general surgeons had a significantly higher leak rate than those reporting to be colorectal surgeons (12.1% vs 7.3%, OR 1.65, 95% CI 1.04–2.64, P = 0.04). Conclusion This study did not identify any difference in anastomotic leak rates according to the type of stapling device used to close the apical aspect. In addition, oversewing of the anastomotic staple lines appears to confer no benefit in terms of reducing leak rates. Although general surgeons operated on patients with more high?risk characteristics than colorectal surgeons, a higher leak rate for general surgeons which remained after risk adjustment needs further exploration

The relationship between method of anastomosis and anastomotic failure after right hemicolectomy and ileo-caecal resection: an international snapshot audit.

BACKGROUND: Anastomosis technique following right sided colonic resection is widely variable and may affect patient outcomes. This study aimed to assess the association between leak and anastomosis technique (stapled versus handsewn) METHODS: This was a prospective, multicentre, international audit including patients undergoing elective or emergency right hemicolectomy or ileo-caecal resection operations over a two-month period in early 2015. The primary outcome measure was the presence of anastomotic leak within 30 days of surgery, using a pre-specified definition. Mixed effects logistic regression models were used to assess the association between leak and anastomosis method, adjusting for patient, disease and operative cofactors, with centre included as a random effect variable. RESULTS: This study included 3208 patients, of whom 78.4% (n=2515) underwent surgery for malignancy and 11.7% (n=375) for Crohn's disease. An anastomosis was performed in 94.8% (n=3041) of patients, which was handsewn in 38.9% (n=1183) and stapled in 61.1% (n=1858) cases. Patients undergoing handsewn anastomosis were more likely to be emergency admissions (20.5% handsewn versus 12.9% stapled) and to undergo open surgery (54.7% versus 36.6%). The overall anastomotic leak rate was 8.1% (245/3041), which was similar following handsewn (7.4%) and stapled (8.5%) techniques (p=0.3). After adjustment for cofactors, the odds of a leak were higher for stapled anastomosis (adjusted odds ratio 1.43, 95% confidence interval 1.04-1.95, p=0.03). DISCUSSION: Despite being used in lower risk patients, stapled anastomosis was associated with an increased anastomotic leak rate in this observational study. Further research is needed to define patient groups in whom a stapled anastomosis is safe. This article is protected by copyright. All rights reserve

Relationship between method of anastomosis and anastomotic failure after right hemicolectomy and ileo-caecal resection: an international snapshot audit

Aim: The anastomosis technique used following right-sided colonic resection is widely variable and may affect patient outcome. This study aimed to assess the association between leak and anastomosis technique (stapled vs handsewn). Method: This was a prospective, multicentre, international audit including patients undergoing elective or emergency right hemicolectomy or ileo-caecal resection operations over a 2-month period in early 2015. The primary outcome measure was the presence of anastomotic leak within 30\ua0days of surgery, determined using a prespecified definition. Mixed effects logistic regression models were used to assess the association between leak and anastomosis method, adjusting for patient, disease and operative cofactors, with centre included as a random-effect variable. Results: This study included 3208 patients, of whom 78.4% (n\ua0=\ua02515) underwent surgery for malignancy and 11.7% (n\ua0=\ua0375) underwent surgery for Crohn's disease. An anastomosis was performed in 94.8% (n\ua0=\ua03041) of patients, which was handsewn in 38.9% (n\ua0=\ua01183) and stapled in 61.1% (n\ua0=\ua01858). Patients undergoing handsewn anastomosis were more likely to be emergency admissions (20.5% handsewn vs 12.9% stapled) and to undergo open surgery (54.7% handsewn vs 36.6% stapled). The overall anastomotic leak rate was 8.1% (245/3041), which was similar following handsewn (7.4%) and stapled (8.5%) techniques (P\ua0=\ua00.3). After adjustment for cofactors, the odds of a leak were higher for stapled anastomosis (adjusted OR\ua0=\ua01.43; 95% CI: 1.04\u20131.95; P\ua0=\ua00.03). Conclusion: Despite being used in lower-risk patients, stapled anastomosis was associated with an increased anastomotic leak rate in this observational study. Further research is needed to define patient groups in whom a stapled anastomosis is safe

Risk factors for unfavourable postoperative outcome in patients with Crohn's disease undergoing right hemicolectomy or ileocaecal resection. An international audit by ESCP and S-ECCO

Aim: Patient- and disease-related factors, as well as operation technique, all have the potential to impact on postoperative outcome in Crohn's disease. The available evidence is based on small series and often displays conflicting results. The aim was to investigate the effect of preoperative and intra-operative risk factors on 30-day postoperative outcome in patients undergoing surgery for Crohn's disease. Method: This was an international prospective snapshot audit including consecutive patients undergoing right hemicolectomy or ileocaecal resection. The study analysed a subset of patients who underwent surgery for Crohn's disease. The primary outcome measure was the overall Clavien\u2013Dindo postoperative complication rate. The key secondary outcomes were anastomotic leak, reoperation, surgical site infection and length of stay in hospital. Multivariable binary logistic regression analyses were used to produce odds ratios and 95% confidence intervals. Results: In all, 375 resections in 375 patients were included. The median age was 37 and 57.1% were women. In multivariate analyses, postoperative complications were associated with preoperative parenteral nutrition (OR 2.36, 95% CI 1.10\u20134.97), urgent/expedited surgical intervention (OR 2.00, 95% CI 1.13\u20133.55) and unplanned intra-operative adverse events (OR 2.30, 95% CI 1.20\u20134.45). The postoperative length of stay in hospital was prolonged in patients who received preoperative parenteral nutrition (OR 31, 95% CI 1.08\u20131.61) and those who had urgent/expedited operations (OR 1.21, 95% CI 1.07\u20131.37). Conclusion: Preoperative parenteral nutritional support, urgent/expedited operation and unplanned intra-operative adverse events were associated with unfavourable postoperative outcome. Enhanced preoperative optimization and improved planning of operation pathways and timings may improve outcomes for patients

Osteocytes: mechanosensors of bone and orchestrators of mechanical adaptation

Significant progress has been made in the field of mechanotransduction in bone cells. The knowledge about the role of osteocytes as the professional mechanosensor cells of bone as well as the lacuno-canalicular porosity as the structure that mediates mechanosensing is increasing. New insights might result in a paradigm for understanding the bone formation response to mechanical loading, and the bone resorption response to disuse. Under physiological loading conditions the strain-derived flow of interstitial fluid through the lacuno-canalicular porosity seems to mechanically activate the osteocytes, which subsequently alter the bone remodeling activity of osteoblasts and/or osteoclasts. Fatigue loading results in local microdamage, disruption of normal flow patterns, and osteocyte apoptosis. Apoptotic osteocytes likely attract osteoclasts to resorb the damaged bone. This concept allows explanation of local bone gain and loss, as well as remodeling in response to fatigue damage, as processes supervised by mechanosensitive osteocytes. Uncovering the cellular and mechanical basis of the osteocyte’s response to loading would greatly contribute to our understanding of the cellular basis for bone remodeling, and could contribute to the discovery of new treatment modalities for bone mass disorders, such as osteoporosis

Relationship between method of anastomosis and anastomotic failure after right hemicolectomy and ileo-caecal resection: an international snapshot audit

Aim The anastomosis technique used following right-sided colonic resection is widely variable and may affect patient outcome. This study aimed to assess the association between leak and anastomosis technique (stapled vs handsewn). Method This was a prospective, multicentre, international audit including patients undergoing elective or emergency right hemicolectomy or ileo-caecal resection operations over a 2-month period in early 2015. The primary outcome measure was the presence of anastomotic leak within 30 days of surgery, determined using a prespecified definition. Mixed effects logistic regression models were used to assess the association between leak and anastomosis method, adjusting for patient, disease and operative cofactors, with centre included as a random-effect variable. Results This study included 3208 patients, of whom 78.4\% (n = 2515) underwent surgery for malignancy and 11.7\% (n = 375) underwent surgery for Crohn's disease. An anastomosis was performed in 94.8\% (n = 3041) of patients, which was handsewn in 38.9\% (n = 1183) and stapled in 61.1\% (n = 1858). Patients undergoing hand-sewn anastomosis were more likely to be emergency admissions (20.5\% handsewn vs 12.9\% stapled) and to undergo open surgery (54.7\% handsewn vs 36.6\% stapled). The overall anastomotic leak rate was 8.1\% (245/3041), which was similar following handsewn (7.4\%) and stapled (8.5\%) techniques (P = 0.3). After adjustment for cofactors, the odds of a leak were higher for stapled anastomosis (adjusted OR = 1.43; 95\% CI: 1.04-1.95; P = 0.03). Conclusion Despite being used in lower-risk patients, stapled anastomosis was associated with an increased anastomotic leak rate in this observational study. Further research is needed to define patient groups in whom a stapled anastomosis is safe